| 1. |
- Blomberg, Marie I., et al.
(författare)
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Maternal Obesity and Morbid Obesity: the Risk for Birth Defects in the Offspring
- 2010
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Ingår i: Birth Defects Research. Part A: Clinical and Molecular Teratology. - : Wiley. - 1542-0760 .- 1542-0752. ; 88:1, s. 35-40
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The objective of this study was to assess, in a large data set from Swedish Medical Health Registries, whether maternal obesity and maternal morbid obesity were associated with an increased risk for various structural birth defects. METHODS: The study population consisted of 1,049,582 infants born in Sweden from January 1, 1995, through December 31, 2007, with known maternal weight and height data. Women were grouped in six categories of body mass index (BMI) according to World Health Organization classification. Infants with congenital birth defects were identified from three sources: the Swedish Medical Birth Registry, the Register of Birth Defects, and the National Patient Register. Maternal age, parity, smoking, and year of birth were thought to be potential confounders and were included as covariates in the adjusted odds ratio analyses. RESULTS: Ten percent of the study population was obese. Morbid obesity (BMI >= 40) occurred in 0.7%. The prevalence of congenital malformations was 4.7%, and the prevalence of relatively severe malformations was 3.2%. Maternal prepregnancy morbid obesity was associated with neural tube defects OR 4.08 (95% CI 1.87-7.75), cardiac defects OR 1.49 (95% CI 1.24-1.80), and orofacial clefts OR 1.90 (95% CI 1.27-2.86). Maternal obesity (BMI >= 30) significantly increased the risk of hydrocephaly, anal atresia, hypospadias, cystic kidney, pes equinovarus, omphalocele, and diaphragmatic hernia. CONCLUSION: The risk for a morbidly obese pregnant woman to have an infant with a congenital birth defect is small, but for society the association is important in the light of the ongoing obesity epidemic. Birth Defects Research (Part A) 88:35-40, 2010. (C) 2009 Wiley-Liss, Inc.
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| 2. |
- Cleary, Brian J., et al.
(författare)
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Early Pregnancy Azathioprine Use and Pregnancy Outcomes
- 2009
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Ingår i: Birth Defects Research. Part A: Clinical and Molecular Teratology. - : Wiley. - 1542-0760 .- 1542-0752. ; 85:7, s. 647-654
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Azathioprine (AZA) is used during pregnancy by h omen with inflammatory bowel disease (IBD), other autoimmune disorders, malignancy, and organ transplantation. Previous studies have demonstrated potential risks. METHODS: The Swedish Medical Birth Register was used to identify 476 women who reported the use of AZA in early pregnancy. The effect of AZA exposure on pregnancy outcomes was Studied after adjustment for maternal characteristics that could act as confounders. RESULTS: The most common indication for AZA use was IBD. The rate of congenital malformations was 6.2% in the AZA group and 4.7% among all infants born (adjusted OR: 1.41, 95% CI: 0.98-2.04). An association between early pregnancy AZA exposure and ventricular/atrial septal defects was found (adjusted OR: 3.18, 95% CI: 1.45-6.04)Exposed infants were also more likely to be preterm, to weigh <2500 gm, and to be small for gestational age compared to all infants born. This effect remained for preterm birth and low birth weight when infants of women with IBD but without AZA exposure were used as a comparison group. A trend toward an increased risk of congenital malformations was found among infants of women with IBD using AZA compared to women with IBD not using AZA (adjusted OR: 1.42, 95% CI: 0.93-2.18). CONCLUSIONS: Infants exposed to AZA in early pregnancy may be at a moderately increased risk of congenital malformations, specifically ventricular/atrial septal defects. There is also an increased risk of growth restriction and preterm delivery. These associations may be confounded by the severity of maternal illness. Birth Defect: Research (Part A) 85:647-654, 2009. (C) 2009 Wiley-Liss, Inc.
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| 3. |
- Cocchi, Guido, et al.
(författare)
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International Trends of Down Syndrome 1993-2004 : Births in Relation to Maternal Age and Terminations of Pregnancies
- 2010
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Ingår i: Birth defects research. Clinical and molecular teratology. - : Wiley. - 1542-0752 .- 1542-0760. ; 88:6, s. 474-479
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this study was to examine trends of Down syndrome (DS) in relation to maternal age and termination of pregnancies (ToP) in 20 registries of the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR). METHODS: Trends of births with DS (live-born and stillborn), ToP with DS, and maternal age (percentage of mothers older than 35 years) were examined by year over a 12-year period (1993-2004). The total mean number of births covered was 1550,000 annually. RESULTS: The mean percentage of mothers older than 35 years of age increased from 10.9% in 1993 to 18.8% in 2004. However, a variation among the different registers from 4-8% to 20-25% of mothers >35 years of age was found. The total mean prevalence of DS (still births, live births, and ToP) increased from 13.1 to 18.2/10,000 births between 1993 and 2004. The total mean prevalence of DS births remained stable at 8.3/10,000 births, balanced by a great increase of ToP. In the registers from France, Italy, and the Czech Republic, a decrease of DS births and a great increase of ToP was observed. The number of DS births remained high or even increased in Canada Alberta, and Norway during the study period. CONCLUSIONS: Although an increase in older mothers was observed in most registers, the prevalence of DS births remained stable in most registers as a result of increasing use of prenatal diagnostic procedures and ToP with DS.
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| 4. |
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| 5. |
- Danielsson, Christian, et al.
(författare)
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Polytherapy with hERG-blocking antiepileptic drugs : Increased risk for embryonic cardiac arrhythmia and teratogenicity
- 2007
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Ingår i: Birth defects research. Clinical and molecular teratology. - : Wiley. - 1542-0752 .- 1542-0760. ; 79:8, s. 595-603
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The antiepileptic drugs (AEDs) phenytoin, phenobarbital, dimethadione, and carbamazepine cause a similar pattern of malformations in humans, with an increased risk after polytherapy. The teratogenicity has been linked to cardiac rhythm disturbances and hypoxic damage as a consequence of their common potential to inhibit a specific potassium ion current (IKr). The IKr is of major importance for embryonic cardiac repolarization and rhythm regulation. This study investigated whether these AEDs cause irregular rhythm and if various combinations of AEDs result in higher arrhythmia risk than exposure to a single AED. METHODS: The effects on heart rhythm of a single AED (monotherapy), and of various combinations (polytherapy) of AEDs, in gestational day 10 C57BL mouse embryos in culture were analyzed and graphically illustrated during a 25 s recording with a digitalization technique. RESULTS: All of the studied AEDs caused increased intervals between heartbeats (resulting in bradycardia) and large variations in the interval between heartbeats (resulting in irregular rhythm) in a concentration-dependent manner in cultured mouse embryos. Dimethadione caused irregular rhythm at concentrations within and phenytoin slightly above the therapeutic ranges. Polytherapy resulted in more substantial prolongation of the mean interval between heartbeats (>60 ms) than monotherapy at clinically relevant concentrations. CONCLUSIONS: The results suggest that polytherapy more than monotherapy causes substantial prolongation of the cardiac repolarization, a marker associated with high risk of developing irregular rhythm during longer exposure periods (days to months). This supports the idea that the increased risk for malformations following polytherapy is linked to an increased risk for cardiac rhythm disturbances.
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| 6. |
- Draaken, Markus, et al.
(författare)
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Classic Bladder Exstrophy: Frequent 22q11.21 Duplications and Definition of a 414 kb Phenocritical Region
- 2014
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Ingår i: Birth Defects Research. Part A: Clinical and Molecular Teratology. - : Wiley. - 1542-0760 .- 1542-0752. ; 100:6, s. 512-517
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Tidskriftsartikel (refereegranskat)abstract
- Background: Classic bladder exstrophy (CBE) is the most common form of the bladder exstrophy and epispadias complex. Previously, we and others have identified four patients with a duplication of 22q11.21 among a total of 96 unrelated CBE patients. Methods: Here, we investigated whether this chromosomal aberration was commonly associated with CBE/bladder exstrophy and epispadias complex in an extended case-control sample. Multiplex ligation-dependent probe amplification and microarray-based analysis were used to identify 22q11.21 duplications in 244 unrelated bladder exstrophy and epispadias complex patients (including 217 CBE patients) and 665 healthy controls. Results: New duplications of variable size were identified in four CBE patients and one control. Pooling of our previous and present data (eight duplications in 313 CBE patients) yielded a combined odds ratio of 31.86 (95% confidence interval, 4.24-1407.97). Array-based sequence capture and high-throughput targeted re-sequencing established that all breakpoints resided within the low-copy repeats 22A to 22D. Comparison of the eight duplications revealed a 414 kb phenocritical region harboring 12 validated RefSeq genes. Characterization of these 12 candidate genes through whole-mount in situ hybridization of mouse embryos at embryonic day 9.5 suggested that CRKL, THAP7, and LZTR1 are CBE candidate genes. Conclusion: Our data suggest that duplication of 22q11.21 increases CBE risk and implicate a phenocritical region in disease formation. (C) 2014 Wiley Periodicals, Inc.
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| 7. |
- Gustafsson, Renata, et al.
(författare)
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Dermatan sulfate epimerase 1 deficient mice as a model for human abdominal wall defects.
- 2014
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Ingår i: Birth Defects Research. Part A: Clinical and Molecular Teratology. - : Wiley. - 1542-0760 .- 1542-0752. ; 100:9, s. 712-720
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Tidskriftsartikel (refereegranskat)abstract
- Dermatan sulfate (DS) is a highly sulfated polysaccharide with a variety of biological functions in extracellular matrix organization and processes such as tumorigenesis and wound healing. A distinct feature of DS is the presence of iduronic acid, produced by the two enzymes, DS-epimerase 1 and 2, which are encoded by Dse and Dsel, respectively.
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| 8. |
- Gustavsson, P, et al.
(författare)
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Grainyhead genes and mammalian neural tube closure
- 2008
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Ingår i: Birth defects research. Part A, Clinical and molecular teratology. - : Wiley. - 1542-0760 .- 1542-0752. ; 82:10, s. 728-735
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Tidskriftsartikel (refereegranskat)
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| 9. |
- Gäreskog, Mattias, et al.
(författare)
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Combined Supplementation of Folic Acid and Vitamin E Diminishes Diabetes-Induced Embryotoxicity in Rats
- 2006
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Ingår i: Birth defects research. Clinical and molecular teratology. - : Wiley. - 1542-0752 .- 1542-0760. ; 76:6, s. 483-490
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Oxidative stress and enhanced apoptosis may be involved in the induction of embryonic dysmorphogenesis in diabetic pregnancy. Administration of folic acid or vitamin E diminishes embryonic dysmorphogenesis. We aimed to evaluate the effect of combined treatment with folic acid and vitamin E on the disturbed development in embryos of diabetic rats. METHODS: Pregnant nondiabetic and diabetic rats were treated with daily injections of 15 mg/kg folic acid or with 5% vitamin E in the diet. A third group received combined treatment. Day 10 and day 11 embryos were evaluated for development and apoptotic profile. RESULTS: We found increased malformations, resorptions, and profound growth retardation in embryos of diabetic rats compared to control embryos. Vitamin E or folic acid alone, or the 2 compounds combined, normalized embryonic demise. Maternal diabetes caused decreased nuclear factor-kappa B (NF-kappa B) activity and B-cell lymphoma 2 (Bcl-2) protein level, and increased Bcl-2-associated x proteins (Bax) in embryos. Supplementation of vitamin E alone normalized the Bax protein level in a diabetic environment. Administration of folic acid to diabetic rats increased NF-kappa B activity and Bcl-2 protein level. Combined treatment normalized Bcl-2 and Bax protein level in a diabetic environment. CONCLUSIONS: Combined supplementation of folic acid and vitamin E to pregnant diabetic rats diminished diabetes-induced malformations and resorptions, concomitant with normalization of apoptotic protein levels. No treatment completely abolished the embryonic demise; therefore, other mechanisms than oxidative stress and apoptosis are likely to be involved in diabetic embryopathy.
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| 10. |
- Källén, Bengt, et al.
(författare)
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Congenital Malformations in Infants Born after In Vitro Fertilization in Sweden
- 2010
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Ingår i: BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY. - : John Wiley andamp; Sons, Ltd. - 1542-0752 .- 1542-0760. ; 88:3, s. 137-143
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The risk for congenital malformations is increased in infants born after in vitro fertilization (IVF). Some specific malformations appear to be more affected than others. METHODS: The presence of congenital malformations in 15,570 infants born after IVF with an embryo transfer between April 1, 2001, and the end of 2006 were compared with all infants born in Sweden during 2001 to 2007 (n = 689,157). Risk estimates were made after adjusting for year of birth, maternal age, parity, smoking, and body mass index. The risks of specific malformations were compared with data from a previous study (1982 to March 31, 2001) of 16,280 infants born after IVF. Different IVF methods were compared to respect to malformation risk. RESULTS: Increased risks of a similar magnitude were found for most cardiovascular malformations and limb reduction defects for both study periods. For neural tube defects, cardiac septal defects, and esophageal atresia, there was still an increased risk, but it was lower during the second than during the first period. For small bowel atresia, anal atresia, and hypospadias, the risk increase observed during the first study period had disappeared during the second period. An increased risk was seen for some syndromes that have been associated with imprinting errors. No difference in malformation risk according to IVF method was apparent. CONCLUSIONS: A slightly increased risk for congenital malformations after IVF persists. A decreasing risk is seen for some specific malformations, either true or the result of multiple testing.
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| 11. |
- Källén, Bengt, et al.
(författare)
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In vitro fertilization (IVF) in Sweden : Risk for congenital malformations after different IVF methods
- 2005
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Ingår i: Birth defects research. Clinical and molecular teratology. - : Wiley. - 1542-0752 .- 1542-0760. ; 73:3, s. 162-169
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The possible excess of congenital malformations in infants born after in vitro fertilization (IVF) has been much discussed in the literature, with controversial conclusions. This population based study is aimed at analyzing the presence of congenital malformations in a large group of infants born after IVF and to compare malformation risk both with that of all infants born and according to IVF method used. METHODS: Infants born after IVF during the period 1982-2001 were ascertained from all IVF clinics in Sweden. The presence of congenital malformations was identified from three national health registers: the Swedish Medical Birth Register, the Swedish Registry of Congenital Malformations, and the Swedish Hospital Discharge Register. The IVF children were compared with all children born in Sweden during the same period and recorded in the Swedish Medical Birth Register. RESULTS: Among 16,280 IVF children (30% conceived after intracytoplasmatic sperm injection [ICSI]) a 42% excess of any congenital malformation was found, explainable by parental characteristics and in some cases by the high rate of multiple births. Among these children, 8% had a congenital malformation, and 15% had a relatively severe condition. For neural tube defects, choanal atresia, and alimentary tract atresia, an additional risk increase was seen. There was no difference in malformation rate according to IVF method except for an excess of hypospadias after ICSI. CONCLUSIONS: An increased risk for congenital malformations occurs after IVF, similar for the different IVF techniques used, and mainly a consequence of parental characteristics. A few specific conditions show an extra increase in risk. © 2005 Wiley-Liss, Inc.
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| 12. |
- Källén, Bengt, et al.
(författare)
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Maternal use of selective serotonin re-uptake inhibitors in early pregnancy and infant congenital malformations.
- 2007
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Ingår i: Birth Defects Research. Part A: Clinical and Molecular Teratology. - : Wiley. - 1542-0760 .- 1542-0752. ; 79:4, s. 301-308
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Maternal use of selective serotonin re-uptake inhibitors (SSRIs) has recently been associated with an increased risk for certain malformations. METHODS: Using the Swedish Medical Birth Register, we identified women who had reported the use of SSRIs in early pregnancy and studied their infants, born between July 1, 1995 and the end of 2004. Congenital malformations were identified from that register, from the Register of Congenital Malformations, and from the Hospital Discharge Register. The effect of drug exposure was studied after adjustment for a number of identified maternal characteristics that could act as confounders. RESULTS: We identified 6,481 women who reported the use of SSRIs in early pregnancy and their 6,555 infants. There was no general increase in malformation risk. An increased risk for cystic kidneys was seen, but this was based on only nine malformed infants, and the pathology varied between these cases. An in-depth study of cardiovascular defects identified an association between such defects and notably ventricular and atrial septum defects and maternal use of paroxetine but not other SSRls. No support for a postulated association between SSRI use and infant craniostenosis or omphalocele was found. CONCLUSIONS: Use of SSRIs in early pregnancy does not seem to be a major risk factor for infant malformations. The association between paroxetine use and infant cardiovascular defects may be a result of multiple testing, but is supported by other studies.
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| 13. |
- Leoncini, Emanuele, et al.
(författare)
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Frequency of holoprosencephaly in the International Clearinghouse Birth Defects Surveillance Systems : Searching for population variations.
- 2008
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Ingår i: Birth defects research. Clinical and molecular teratology. - : Wiley. - 1542-0752 .- 1542-0760. ; 82:8, s. 585-591
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Holoprosencephaly (HPE) is a developmental field defect of the brain that results in incomplete separation of the cerebral hemispheres that includes less severe phenotypes, such as arhinencephaly and single median rnaxillary central incisor. Information on the epidemiology of HPE is limited, both because few population-based studies have been reported, and because small Studies must observe a greater number of years in order to accumulate sufficient numbers of births for a reliable estimate. METHODS: We collected data from 2000 through 2004 from 24 of the 46 Birth Defects Registry Members of the International Clearinghouse for Birth Defects Surveillance and Research. This Study is based on more than 7 million births in various areas from North and South America, Europe, and Australia. RESULTS: A total of 963 HPE cases were registered, yielding an overall prevalence of 1.31 per 10,000 births. Because the estimate was heterogeneous, possible causes of variations among populations were analyzed: random variation, Under-reporting and over-reporting bias, variation in proportion of termination of pregnancies among all registered cases and real differences among populations. CONCLUSIONS: The data do not suggest large differences in total prevalence of HPE among the studied Populations that would be useful to generate etiological hypotheses.
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| 14. |
- Niklasson, Bo, et al.
(författare)
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Association of zoonotic Ljungan virus with intrauterine fetal deaths
- 2007
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Ingår i: Birth defects research. Clinical and molecular teratology. - : Wiley. - 1542-0752 .- 1542-0760. ; 79, s. 488-493
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It has recently been shown that Ljungan virus (LV) is associated with disease in its wild rodent reservoir. In addition, it has been demonstrated that LV causes malformations and perinatal death in a mouse model. The question was therefore raised whether LV is a zoonotic agent in humans. METHODS: Population fluctuations of native rodents in Sweden were compared to the incidence of intrauterine fetal deaths (IUFDs) using the Swedish national hospitalization database. Formalin-fixed tissues from cases of IUFD were investigated using LV-specific immunohistochemistry. RESULTS: Variation in the incidence of IU-FDs closely tracked the fluctuations in native rodent populations. LV was detected in the brain tissue in 4 of 10 cases of IUFDs investigated by immunochemistry. LV was also detected in the placenta in 5 of the 10 IUFD cases, but in none of 20 placentas from normal pregnancies. CONCLUSIONS: LV may play an important role in IUFDs.
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| 15. |
- Niklasson, Bo, et al.
(författare)
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Zoonotic Ljungan Virus Associated with Central Nervous System Malformations in Terminated Pregnancy
- 2009
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Ingår i: Birth defects research. Clinical and molecular teratology. - : Wiley. - 1542-0752 .- 1542-0760. ; 85:6, s. 542-545
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Ljungan virus (LV) has been shown to cause central nervous system malformations in laboratory mouse models. The LV has also been associated with intrauterine fetal death in humans. We investigated the presence of LV in a series of human hydrocephaly and anencephaly cases from elective abortions. METHODS: A series of elective abortions owing to hydrocephaly, anencephaly, and similarly aged trisomy 21 elective abortions as controls were examined for LV by immunohistochemistry and real time RTPCR. A second experiment involved newborn mice exposed to LV. RESULTS: LV was diagnosed in 9 of 10 cases with hydrocephalus and in I of 18 trisomy 21 controls by immunohistochemistry. Five of nine cases with anencephaly had a positive PCR result, whereas none of the 12 trisomy 21 available for PCR testing had a positive result. The 47 newborn mice exposed to LV all developed encephalitis, with eight having hydrocephalus. None of the 52 control animals had encephalitis or hydrocephalus. CONCLUSION: The association between LV and both hydrocephaly and anencephaly suggests that LV may be playing an important role in central nervous system malformations in humans. Birth Defects Research (Part A) 85:542-545, 2009, (C) 2009 Wiley-Liss, Inc.
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| 16. |
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| 17. |
- Roest, Pauline A. M., et al.
(författare)
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Exposure of neural crest cells to elevated glucose leads to congenital heart defects, an effect that can be prevented by N-acetylcysteine
- 2007
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Ingår i: Birth defects research. Clinical and molecular teratology. - : Wiley. - 1542-0752 .- 1542-0760. ; 79:3, s. 231-235
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Diabetes mellitus during pregnancy increases the risk for congenital heart disease in the offspring. The majority of the cardiovascular malformations occur in the outflow tract and pharyngeal arch arteries, where neural crest cells are essential for normal development. We studied the effects of specific exposure of neural crest cells to elevated glucose on heart development. Antioxidants reduce the damaging effect of glucose on neural crest cells in vitro; therefore, we investigated the effect of supplementing N-acetylcysteine in vivo. METHODS: Cardiac neural crest of HH 8-12 chicken embryos was directly exposed by a single injection in the neural tube with 30 mM D-glucose (or 30 mM L-glucose as a control). To examine the effect of a reduction in oxidative stress, we added 2 mM N-acetylcysteine to the injected D-glucose. RESULTS: Exposure of neural crest cells to elevated D-glucose-induced congenital heart malformations in 82% of the embryos. In the embryos injected with L-glucose, only 9% developed a heart malformation. As expected, all malformations were located in the outflow tract and pharyngeal arch arteries. The frequency of heart malformations decreased from 82% to 27% when 2 mM N-acetylcysteine was added to the injected D-glucose. CONCLUSIONS: These data are the first to confirm that the vulnerability of neural crest cells to elevated glucose induces congenital heart malformations. The fact that N-acetylcysteine limits the teratogenicity of glucose implies that its damaging effect is mediated by an increase of oxidative stress in the neural crest cells.
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| 18. |
- Samsioe, Annika, et al.
(författare)
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Ljungan Virus Present in Intrauterine Fetal Death Diagnosed by Both Immunohistochemistry and PCR
- 2009
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Ingår i: Birth defects research. Clinical and molecular teratology. - : Wiley. - 1542-0752 .- 1542-0760. ; 85:3, s. 227-229
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Following up on prior evidence from animal and human studies of Ljungan virus (LV) in intrauterine fetal death (IUFD), we examine additional cases of IUFD using two standard assays of viral detection: immunohistochemistry (IHC) and real time RT-PCR. MATERIALS AND METHODS: Frozen and formalin-fixed specimens from IUFD cases were tested for the presence of LV using real time RT-PCR and IHC, respectively. Formalin-fixed organs from terminated pregnancies diagnosed as trisomy 21 were used as controls in the IHC assay. RESULTS: Presence of LV was demonstrated in all five IUFD cases by IHC and further confirmed in. three of these cases by real time RT-PCR. Only one of 18 trisomy 21 controls was LV positive by IHC. CONCLUSION: The presence of LV in IUFD patients has been confirmed by two different assays. Birth Defects Research (Part A) 85:227-229, 2009. (C) 2009 Wiley-Liss, Inc.
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| 19. |
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| 20. |
- Wentzel, Parri, et al.
(författare)
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A diabetes-like environment increases malformation rate and diminishes prostaglandin E(2) in rat embryos : reversal by administration of vitamin E and folic acid
- 2005
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Ingår i: Birth defects research. Clinical and molecular teratology. - : Wiley. - 1542-0752 .- 1542-0760. ; 73:7, s. 506-511
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Offspring of women with diabetes are at increased risk for congenital malformations and disturbed growth compared with infants from nondiabetic pregnancies. The precise biological process behind these effects is not yet completely clarified. Previous studies have suggested that diabetic embryopathy is associated with increased level of oxidative stress and disturbed arachidonic acid metabolism. The aim of the present study was to investigate whether a diabetes-like environment both in vivo and in vitro increases embryonic levels of isoprostanes and alters embryonic prostaglandin E(2) (PGE(2)) concentration. Furthermore, we studied whether vitamin E and folic acid treatment rectify such alterations. METHODS: Embryos from diabetic and nondiabetic rats at gestational days (GDs) 10 and 11 were used. In the in vitro experiments, we used whole embryo culture, which mimics pregnancy. GD 9 embryos from nondiabetic rats were cultured for either 24 hr (corresponding to GD 10) or 48 hr (corresponding to GD 11) and exposed to 10 or 30 mM glucose concentration with or without folic acid. RESULTS: Embryos from diabetic rats and embryos cultured in a high glucose concentration showed increased malformation rates. Dietary treatment with vitamin E in vivo and supplementation of folic acid in the culture medium with 30 mM glucose in vitro decreased the malformation rate, decreased embryonic isoprostane levels, and increased PGE(2) concentration. CONCLUSIONS: Diabetes-induced oxidative stress and disturbance of PGE(2) production may contribute to the embryonic dysmorphogenesis in the offspring of diabetic rodents and, thereby, may also have a role in human diabetic embryopathy.
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| 21. |
- Greenlees, Ruth, et al.
(författare)
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Paper 6: EUROCAT Member Registries: Organization and Activities
- 2011
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Ingår i: Birth Defects Research Part C: Embryo Today: Reviews. - : Wiley. - 1542-975X. ; 91:Suppl. 1, s. 51-100
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: EUROCAT is a network of population-based congenital anomaly registries providing standardized epidemiologic information on congenital anomalies in Europe. There are three types of EUROCAT membership: full, associate, or affiliate. Full member registries send individual records of all congenital anomalies covered by their region. Associate members transmit aggregate case counts for each EUROCAT anomaly subgroup by year and by type of birth. This article describes the organization and activities of each of the current 29 full member and 6 associate member registries of EUROCAT. METHODS: Each registry description provides information on the history and funding of the registry, population coverage including any changes in coverage over time, sources for ascertaining cases of congenital anomalies, and upper age limit for registering cases of congenital anomalies. It also details the legal requirements relating to termination of pregnancy for fetal anomalies, the definition of stillbirths and fetal deaths, and the prenatal screening policy within the registry. Information on availability of exposure information and denominators is provided. The registry description describes how each registry conforms to the laws and guidelines regarding ethics, consent, and confidentiality issues within their own jurisdiction. Finally, information on electronic and web-based data capture, recent registry activities, and publications relating to congenital anomalies, along with the contact details of the registry leader, are provided. CONCLUSIONS: The registry description gives a detailed account of the organizational and operational aspects of each registry and is an invaluable resource that aids interpretation and evaluation of registry prevalence data. Birth Defects Research (Part A) 91: S51-S100, 2011. (C) 2011 Wiley-Liss, Inc.
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| 22. |
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| 23. |
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| 24. |
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| 25. |
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| 26. |
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| 27. |
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| 28. |
- Miller, Marilyn T., et al.
(författare)
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Thalidomide and Misoprostol: Ophthalmologic Manifestations and Associations Both Expected and Unexpected
- 2009
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Ingår i: BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY. - : Wiley. - 1542-0752. ; 85:8, s. 667-676
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Forskningsöversikt (refereegranskat)abstract
- Thalidomide is a very potent teratogen capable of causing severe systemic malformations if the fetus is exposed during the sensitive period. Although structural anomalies of the eye can occur from thalidomide exposure, the most frequent eye complication is secondary to damage to the cranial nuclei in the brain stem, resulting in aberrant neurologic connections causing a condition of abnormal ocular movement, Duane syndrome. A less frequent anomalous neurologic complication is tearing when eating (paradoxical gustolacrimal tearing or crocodile tears) or lack of emotional tearing. The involvement of the 6th and 7th cranial nerves, often seen together in the thalidomide-affected individual, is also characteristic of Möbius syndrome/sequence. This syndrome usually occurs sporadically, but characteristic findings of this condition have also been observed in South American children who were born after an unsuccessful attempt to induce abortion with the prostaglandin drug misoprostol (Cytotec©). Aberrant tearing also occurs in some individuals with Möbius syndrome. Autism spectrum disorder (ASD), an unexpected associated finding in a Swedish thalidomide study, is now also noted in Möbius studies, in patients both with and without exposure to misoprostol. Birth Defects Research (Part A) 2009.
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| 29. |
- Molin, Daniël G M, et al.
(författare)
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Disturbed morphogenesis of cardiac outflow tract and increased rate of aortic arch anomalies in the offspring of diabetic rats
- 2004
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Ingår i: Birth Defects Research. Part A. Clinical and Molecular Teratology. - 1542-0752. ; 70:12, s. 927-938
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Maternal diabetes (MD) is a risk factor for offspring to develop cardiovascular anomalies; this is of growing clinical concern since the number of women in childbearing age with compromised glucose homeostasis is increasing. Hyperglycemia abrogates cardiovascular development in vitro; however, a link to cardiovascular defects in diabetic offspring remains to be investigated. METHODS: We have studied cardiovascular development in offspring of MD rats by examining serial histological sections of GD 12.0-18.0 offspring. Development of pharyngeal arch artery malformations was analyzed and related to intracardiac anomalies. RESULTS: Pharyngeal arch artery and intracardiac defects were present in 27 of 37 MD GD 13.0-18.0 offspring. Early sixth arch arteries showed abrogated arteriogenesis, whereas fourth arch artery defects developed as a result of abnormal remodeling. Morphometrical analysis showed increased apoptosis in regressing artery segments and reduced apoptosis in persisting artery segments. Double outlet right ventricle with infundibular stenosis (tetralogy of Fallot) was predominantly found in combination with sixth artery defects and pulmonary atresia. As confirmed by morphometric analysis and three-dimensional (3D)-reconstructions, outflow tract defects coincided with endocardial cushion hypoplasia. Cases with teratology of Fallot additionally showed a shorter outflow tract. No relation with apoptosis or disturbed neural crest cell migration was found. CONCLUSIONS: Our data uniquely demonstrate mechanistic differences involved in the development of sixth and fourth artery anomalies. Whereas increased apoptosis induces fourth artery anomalies, pulmonary outflow obstruction abrogates sixth artery differentiation independent of apoptosis. The model presented allows analysis of diabetic conditions on cardiovascular development in vivo, essential for elucidating this teratology.
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- Strömland, Kerstin, 1934, et al.
(författare)
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Fetal Alcohol Spectrum Disorders among Children in a Brazilian Orphanage
- 2015
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Ingår i: Birth Defects Research Part a-Clinical and Molecular Teratology. - : Wiley. - 1542-0752. ; 103:3, s. 178-185
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Tidskriftsartikel (refereegranskat)abstract
- Background: The objective was to investigate the frequency of fetal alcohol spectrum disorders (FASD) and ophthalmologic anomalies in orphanage children in Brazil. Methods: A prospective study was performed on 94 children living in an orphanage in Brazil. The children were examined by a multidisciplinary team consisting of specialists in pediatrics, neurology, psychology, neuropsychiatry, and ophthalmology. Results: The main reasons for living in the orphanage, in 61% of the children, were negligence, child abuse, and abandonment. Of all the children studied, 50% had mothers with known alcohol abuse and 47% had one or more diagnoses of neurodevelopmental/behavioral and/or cognitive deficits. General developmental delay was found in 18%, intellectual disability in 3%, cognitive impairment in 27%, attention-deficit/hyperactivity disorder in 14%, and autism in 3%. Altogether 17% had FASD, comprising three children with fetal alcohol syndrome (FAS), six with partial FAS, and seven with alcohol-related neurodevelopmental disorder. 16% had ophthalmological findings such as poor vision, strabismus, and dysmorphology of the optic nerves. Twenty-eight children (30%) were adopted from the orphanage; of these, six had FASD (two FAS, three partial FAS, one alcohol-related neurodevelopmental disorder), five had attention-deficit/hyperactivity disorder, and eight had developmental delay. Conclusion: Nearly half of the children living in the orphanage had neurodevelopmental disorders and a considerable number showed signs of damage from prenatal alcohol exposure. A broader look at the problem of FASD in Brazil and other South American countries is desirable to document the burden of disease and provide data for targeting prevention efforts. Birth Defects Research (Part A) 103:178-185, 2015. (c) 2014 Wiley Periodicals, Inc.
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